Nicotine is the psychoactive component of tobacco that is the principal reinforcing agent in cigarette smoking. While considerable work has been done on the potential health effects of smoking, little is known about the contribution of nicotine to those effects. Although cigarette smoke, composed of approximately 3800 components, has been shown to alter immune function, the immunological effects of nicotine administered in vivo has not been determined. Recent developments in the treatment of smoking cessation, including the use of nicotine gum and patches, has greatly increased the need for studies that examine nicotine's effects on the immune system. In addition, the potential contribution of these effects to the onset of AIDS in HIV-infected individuals exposed to tobacco smoke or nicotine and to the susceptibility of an individual to be infected with the HIV virus, remains to be determined. The objective of this proposal is to expand on our initial data, that which suggests that acute and chronic treatment with nicotine can alter the immune system of rats. Specifically, we will: l) examine a fuller complement of immune measures in a wider array of immunologically relevant tissues in both male and female rats treated both acutely and chronically with nicotine; 2) determine the effects of acute and chronic nicotine treatment on the development of an immune response to a specific antigen; 3) investigate nicotine's effects when administered acutely and chronically on the development of an autoimmune disorder, adjuvant arthritis; 4) employ central and/or systemic administration of nicotinic antagonists to determine whether nicotine's Immunological effects are due to its antigenic nature or to its central and/or peripheral Pharmacological action; 5) analyze the mechanism of nicotine's immunological effects by using Surgical and/or Pharmacological blockade of the opiate, peripheral catecholamine, and hypothalamic- pituitary-adrenocortical systems to determine whether these systems are involved in the mediation of nicotine's immunological effects; and 6) begin investigation of the interaction between the immunological effects of stress and nicotine.